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      Diagnosis of severe respiratory infections in immunocompromised patients

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          Abstract

          An increasing number of critically ill patients are immunocompromised. Acute hypoxemic respiratory failure (ARF), chiefly due to pulmonary infection, is the leading reason for ICU admission. Identifying the cause of ARF increases the chances of survival, but may be extremely challenging, as the underlying disease, treatments, and infection combine to create complex clinical pictures. In addition, there may be more than one infectious agent, and the pulmonary manifestations may be related to both infectious and non-infectious insults. Clinically or microbiologically documented bacterial pneumonia accounts for one-third of cases of ARF in immunocompromised patients. Early antibiotic therapy is recommended but decreases the chances of identifying the causative organism(s) to about 50%. Viruses are the second most common cause of severe respiratory infections. Positive tests for a virus in respiratory samples do not necessarily indicate a role for the virus in the current acute illness. Invasive fungal infections ( Aspergillus, Mucorales, and Pneumocystis jirovecii) account for about 15% of severe respiratory infections, whereas parasites rarely cause severe acute infections in immunocompromised patients. This review focuses on the diagnosis of severe respiratory infections in immunocompromised patients. Special attention is given to newly validated diagnostic tests designed to be used on non-invasive samples or bronchoalveolar lavage fluid and capable of increasing the likelihood of an early etiological diagnosis.

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          The online version of this article (10.1007/s00134-019-05906-5) contains supplementary material, which is available to authorized users.

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          Most cited references88

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          Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.

          Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.
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            Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET).

            Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking. The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts. During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005. We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies.
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              Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database.

              The incidence and epidemiology of invasive fungal infections (IFIs), a leading cause of death among hematopoeitic stem cell transplant (HSCT) recipients, are derived mainly from single-institution retrospective studies. The Transplant Associated Infections Surveillance Network, a network of 23 US transplant centers, prospectively enrolled HSCT recipients with proven and probable IFIs occurring between March 2001 and March 2006. We collected denominator data on all HSCTs preformed at each site and clinical, diagnostic, and outcome information for each IFI case. To estimate trends in IFI, we calculated the 12-month cumulative incidence among 9 sequential subcohorts. We identified 983 IFIs among 875 HSCT recipients. The median age of the patients was 49 years; 60% were male. Invasive aspergillosis (43%), invasive candidiasis (28%), and zygomycosis (8%) were the most common IFIs. Fifty-nine percent and 61% of IFIs were recognized within 60 days of neutropenia and graft-versus-host disease, respectively. Median onset of candidiasis and aspergillosis after HSCT was 61 days and 99 days, respectively. Within a cohort of 16,200 HSCT recipients who received their first transplants between March 2001 and September 2005 and were followed up through March 2006, we identified 718 IFIs in 639 persons. Twelve-month cumulative incidences, based on the first IFI, were 7.7 cases per 100 transplants for matched unrelated allogeneic, 8.1 cases per 100 transplants for mismatched-related allogeneic, 5.8 cases per 100 transplants for matched-related allogeneic, and 1.2 cases per 100 transplants for autologous HSCT. In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis. Understanding the epidemiologic trends and burden of IFIs may lead to improved management strategies and study design.
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                Author and article information

                Contributors
                elie.azoulay@aphp.fr
                Journal
                Intensive Care Med
                Intensive Care Med
                Intensive Care Medicine
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0342-4642
                1432-1238
                7 February 2020
                2020
                : 46
                : 2
                : 298-314
                Affiliations
                [1 ]GRID grid.50550.35, ISNI 0000 0001 2175 4109, Médecine Intensive et Réanimation, , APHP, Saint-Louis Hospital and Paris University, ; Paris, France
                [2 ]GRID grid.5842.b, ISNI 0000 0001 2171 2558, Université de Paris, ; Paris, France
                [3 ]GRID grid.5254.6, ISNI 0000 0001 0674 042X, Department of Intensive Care, Rigshospitalet and Copenhagen Academy for Medical Simulation and Education, , University of Copenhagen, ; Copenhagen, Denmark
                [4 ]GRID grid.29857.31, ISNI 0000 0001 2097 4281, Division of Pulmonary and Critical Care, , Penn State University College of Medicine, ; Hershey, PA USA
                [5 ]GRID grid.429705.d, ISNI 0000 0004 0489 4320, Department of Critical Care, , King’s College Hospital NHS Foundation Trust, ; London, UK
                [6 ]GRID grid.66875.3a, ISNI 0000 0004 0459 167X, Division of Pulmonary and Critical Care Medicine, , Mayo Clinic, ; Rochester, MN USA
                [7 ]GRID grid.10772.33, ISNI 0000000121511713, Polyvalent Intensive Care Unit, Hospital de São Francisco Xavier, NOVA Medical School, , New University of Lisbon, ; Lisbon, Portugal
                [8 ]GRID grid.411375.5, ISNI 0000 0004 1768 164X, Intensive Care Clinical Unit, , Hospital Universitario Virgen Macarena, ; Seville, Spain
                [9 ]GRID grid.416409.e, ISNI 0000 0004 0617 8280, Department of Intensive Care Medicine, , Multidisciplinary Intensive Care Research Organization (MICRO), St. James’s Hospital, ; St James Street, Dublin 8, Ireland
                [10 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Department of Medicine and Interdepartmental Division of Critical Care Medicine, Sinai Health System, , University of Toronto, ; Toronto, ON Canada
                [11 ]GRID grid.411714.6, ISNI 0000 0000 9825 7840, Department of Intensive Care, , Glasgow Royal Infirmary, ; Glasgow, UK
                [12 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Department of Medicine I, Intensive Care Unit 13i2, Comprehensive Cancer Center, Center of Excellence in Medical Intensive Care (CEMIC), , Medical University of Vienna, ; Vienna, Austria
                [13 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), , Instituto Salud Carlos III, ; Madrid, Spain
                [14 ]GRID grid.430994.3, ISNI 0000 0004 1763 0287, CRIPS Department, , Vall d’Hebron Institut of Research (VHIR), ; Barcelona, Spain
                [15 ]GRID grid.418443.e, ISNI 0000 0004 0598 4440, Critical Care Department, , Institut Paoli Calmettes, ; Marseille, France
                Author information
                http://orcid.org/0000-0002-8162-1508
                Article
                5906
                10.1007/s00134-019-05906-5
                7080052
                32034433
                3b7f2841-6ab5-4908-8217-9fb92cc79016
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 20 November 2019
                : 19 December 2019
                Categories
                Review
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Emergency medicine & Trauma
                pneumocystis pneumonia,influenza,aspergillosis,mucormycosis,toxoplasmosis,cytomegalovirus

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